The present invention provides novel compositions of matter and a method for their production. In particular the present invention provides certain 9,11-halo-9,11-dideoxy-PGF-type compounds, which are disclosed herein as structural and pharmacological analogs of naturally-occurring prostaglandin F compounds (e.g., prostaglandin F.sub.1 .alpha., prostaglandin F.sub.2 .alpha., and prostaglandin F.sub.3 .alpha.).
The prostaglandins, as well as numerous of their structural analogs, are known in the art as extremely potent pharmacological agents, rendering them useful for a wide variety of pharmacological purposes.
Such prostaglandins and prostaglandin analogs can be characterized as derivatives of prostanoic acid which has the following structural formula and carbon atom numbering. ##STR1##
With reference to the above formula, the broken line attachments refer to substituents in the alpha configuration, i.e., below the plane of the cyclopentane ring and heavy solid lines indicate substituents in the beta configuration, i.e., above the plane of the cyclopentane ring. Moreover, the use of wavy lines herein (.about.) will represent attachment of substituents in each of the alpha or beta configuration or alternatively attachment in a mixture of alpha and beta configurations.
The prostaglandins, such as PGF.sub.2 .alpha., i.e., ##STR2## exhibit hydroxylation at the C-15 position of the 12-beta side chain. This side chain hydroxyl at C-15 of PGF.sub.2.alpha. is in the S configuration. As used herein expressions such as C-15 and the like refer to the carbon atom in a prostaglandin or prostaglandin analog which is in the position corresponding to the position of the same number in prostanoic acid.
Molecules of the prostaglandins, having several centers of asymmetry, can exist in either racemic or optically active forms. Of the two enantiomeric forms of the prostaglandins, the formulas herein make reference to that enantiomeric form which is of the same stereochemical configuration as prostaglandins obtained from mammalian sources. See for example Bergstrom, et al., Pharmacological Review 20:1 (1968).
Moreover, formulas describing prostaglandin analogs herein shall refer to the enantiomeric form of such analogs which are of the same relative configuration as the prostaglandins obtained from mammalian tissues.
Further, for convenience hereafter the term prostaglandin or "PG" will mean the optically active form of the prostaglandin thereby referred to with the same absolute configuration as obtained from mammalian sources. When reference is made to a racemic form of such prostaglandins, the word "racemic" or "dl" will precede the prostaglandin name. The term "prostaglandin-type" (PG-type) product as used herein will refer to any cyclopentane derivative which is useful for pharmacological purposes. The term "prostaglandin-type intermediate," as used herein, refers to any cyclopentane derivative useful in preparing a prostaglandin-type product. The term "prostaglandin analog" as used herein represents that stereoisomer of a prostaglandin-type product which is of the same relative configuration as the corresponding prostaglandin obtained from mammalian tissues or a mixture comprising such stereoisomers and its enantiomer. In particular, where a formula is used to depict a prostaglandin-type compound herein, the term "prostaglandin analog" refers to the compound of that formula or a mixture comprising that compound and the enantiomer thereof.
Numerous prostaglandins and prostaglandin analogs are known in the art, including prostaglandin analogs wherein the hydrogen present at C-2, C-9, C-14, and C-16, for example, has been replaced by halogen. See, for example, U.S. Pat. No. 4,021,477, describing 14-halo prostaglandin analogs; U.S. Pat. No. 3,997,587, describing 9-fluoro prostaglandin analogs; U.S. Pat. No. 3,001,300, describing 2-fluoro prostaglandin analogs; and U.S. Pat. No. 3,962,293, describing 16-fluoro prostaglandin analogs. See also U.S. Pat. No. 3,755,426 (10-halo-PG's).